The invention relates generally to a mixture of antioxidants and, more specifically, to lipid-soluble formulations that contain a mixture of both lipid- and water-soluble antioxidants.
Lipid autoxidation is the chemical term for a series of destructive processes that readily occur in organic materials by the reaction with molecular oxygen (Lipid Oxidation, E. N. Frankel, Chapter 1, The Oily Press, Dundee, 1998). There are three separate steps in the lipid autoxidation scheme. In the first step (initiation phase) free radicals are gradually formed. Radicals can be formed spontaneously or they can be produced by the thermal or metal catalyzed decomposition of hydroperoxides. The initiation phase in lipid oxidation mainly depends on the fatty acid composition expressed by the degree of unsaturation and the level of metal contamination. In the second step or propagation phase free radicals react with oxygen to form peroxyl radicals. The rate of oxidation accelerates which indicates the autocatalytic nature of the reaction. There is a rapid absorption of molecular oxygen and peroxides are progressively formed. The third step or termination phase, comprises the recombination of various radical species and the lipid autoxidation reaction slows down.
Oils and fats are major constituents in human and animal nutrition. Due to the autoxidation process, lipids will become rancid and undesirable flavor and odor components will be formed. Oxidized oils and fats will become unpalatable and the ingestion of highly oxidized vegetable fat results in a loss of appetite. In addition lipid oxidation will result in a rapid destruction of vitamins and other dietary components reducing the nutritional value of the food and feed matrix. Taking into account all these factors, it is important that effective measures are taken to stabilize oils and fats against oxidation.
The lipid autoxidation process of oils and fats can be delayed by phenolic antioxidants (Lipid Oxidation, E. N. Frankel, Chapter 8, The Oily Press, Dundee, 1998). Inhibition of the free radical autoxidation process by antioxidants is of considerable importance to preserve lipids from oxidative deterioration. Antioxidants inhibit or delay lipid oxidation by capturing lipid radicals and peroxyl radicals. Phenolic compounds with bulky alkyl substituents are effective chain breaking antioxidants because they produce stable and unreactive antioxidant radicals. These antioxidant radicals do not have enough energy to react with the fat to form new free radicals and therefore these antioxidants are called free radical scavengers or primary antioxidants.
Over the past decades especially, synthetic antioxidants such as BHA, BHT, and ethoxyquin have been used extensively in human food and animal feed. An increased concern regarding the application of these synthetic antioxidants has been observed over the last decades, due to the possible mutagenic and carcinogenic character of these products (Toxicology and Biochemistry of Butylated Hydroxyanisole and Butylated Hydroxytoluene, Journal of the American Oil Chemist's Society, Branen, pp. 59-63, 1975).
There has accordingly been an increased amount of attention directed towards natural antioxidants tocopherols, extract of herbs, spices and hulls (e.g., gallic acid, rosemary, sage and thyme), flavones, carotenoids, anthocyanidins, and others (Lipid Oxidation, E. N. Frankel, Chapter 8, The Oily Press, Dundee, 1998). However these natural antioxidants are more expensive compared to synthetic antioxidants, and in sectors where price is an important issue natural antioxidants are not often used.
In this respect semi-synthetic antioxidants can offer a solution. The most commonly used semi-synthetic antioxidants are esters of gallic acids such as propyl gallate and octyl gallate. The distribution and application of these semi-synthetic antioxidants is becoming more and more important.
However, the production of antioxidant formulations based on natural and semi-synthetic antioxidants is more difficult. Generally, those phenolic compounds, such as gallic acid and derivatives, flavones, phenolic di- and tri-terpenes, extract from sage, rosemary, thyme, and others, consist of polar groups which do not dissolve in a lipid system. While these antioxidants dissolve in a polar carrier, such as monopropylene glycol, glycerol, water, and others, such a polar carrier does not dissolve in an apolar lipid system. Mixing of an antioxidant formulation based on such a polar carrier in a lipophillic matrix immediately results in the separation of the antioxidant formulation and a homogeneous distribution of the antioxidant formulation is not achieved.
The inclusion of a metal chelator such as citric acid, phosphoric acid, and others in an antioxidant formulation is advantageous for its metal chelating activity (Lipid Oxidation, E. N. Frankel, Chapter 7, The Oily Press, Dundee, 1998). However, metal chelators only dissolve in polar solvents as well. As a consequence it is a challenge to formulate an antioxidant formulation which combines the inclusion of a metal chelator with oil solubility.
Due to the hydrophilic groups present in phenolic compounds and metal chelators they are either totally insoluble or very sparsely soluble in fatty systems. These polar compounds can be rendered fat-soluble by several methodologies.
The traditional procedure to render polar compounds lipid soluble is by synthesis (Drug Formulation, I. Racz, Chapter 4, John Wiley and Sons, 1989 and Dufour et al. J. Agric. Food Chem., 2002, 50, pp. 3425-3430). This is carried out by addition of an aliphatic side chain in order to increase the lipophylic character of the product. Esterification with a suitable fatty acid is a common practice to increase the lipid solubility. For example propyl gallate, octyl gallate and dodecyl gallate are derived from gallic acid and ascorbyl palmitate is derived from ascorbic acid. While these derived compounds have significantly increased lipid solubility, long mixing times at elevated temperatures are still required in order to make these compounds completely soluble into an oil and fat matrix.
Liposomes have also been used to introduce polar compounds into an oil and fat system. Liposomes consist of one or more concentric spheres of lipid bilayers surrounding an aqueous compartment. If liposomes are incorporated in a fatty system, the hydrophilic compounds remain separated from the fatty system because the hydrophilic compounds do not dissolve and are present as a heterogeneous dispersion. The use and success of liposomes has been rather limited (see “Drug Targeting and Delivery”, Chapter 6, edited by H. E. Junginger, Ellis Horwood 1992).
Another possibility is the formation of solid antioxidant particles of small particle size (e.g. micron size), which suspend easily in oils and fats. This procedure has been carried out with ascorbyl palmitate (U.S. Pat. No. 5,314,686).
A variety of commercial products are available, but none have the advantages of the present antioxidant system. Oxitrap ME (Nordos, Belgium) is a product based on BHA, propyl gallate and fatty acids esterified with citric acid. This product does not contain a synergistic combination with other gallates. Gallic acid itself will not dissolve in this type of product. Citric acid is present as an ester, which significantly reduces the chelating activity.
Loxidan TL 400 (Lohmann Animal Health GmbH, Germany) is a product that contains 26% ethoxyquin, 7% propyl gallate and 4% citric acid. Again this is a formulation is without a synergistic combination with other gallates. The formulation contains ethoxyquin, an antioxidant that can also function in part as a solvent for gallates. Formulations without ethoxyquin will be less effective in dissolving propyl gallate and citric acid. This limits the application because ethoxyquin is becoming less widely accepted.
Eurotiox L32 (Eurotec Nutrition, S.I., Spain) is a product that contains BHA, citric acid and propyl gallate, but the solvent is polyethylene glycol, which is not allowed in the European Union. This formulation has no synergistic combination with other gallates.
Ban-ox (Alltech, Inc., U.S.) is a product that does not contain a synergistic combination of gallates. This product also contains high amounts of iso-propanol, a flammable compound. Most antioxidants are used during the processing of fats and oils. This processing often occurs at higher temperatures, which means that flammable formulations cannot be used.
Liquid antioxidant formulations have been used for a long time in the food and feed industry. A liquid antioxidant formulation has the advantage of dissolving easily into the lipid system. The carrier used in an antioxidant formulation should dissolve the antioxidant in a considerable concentration (generally up to 10-30% antioxidant) and upon introduction into the lipid system disperse easily. An antioxidant formulation based on BHT or BHA can easily be based on a vegetable oil as carrier with good solubility in an oil system.
There has been a need in the market for an antioxidant formulation that could protect vegetable oils more efficiently than the current available formulations. This need is particularly important in the European Union because the use of animal fats in feed production decreased very rapidly after the “Mad Cow Disease” (bovine spongiform encephalitis) crisis in Europe. Feed ingredients from an animal source were replaced with ingredients from a vegetable source. Because vegetable oils are more unsaturated, an antioxidant formulation that was especially potent in this type of lipid matrix was needed.